中国药学杂志

肿瘤微环境中脂代谢与卵巢癌PARPi耐药相关机制的研究进展

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陈韦唯 ¹^,²^,³ , 王琪 ¹^,²^,³^,^*

中国药学杂志 | 综述 2025,60(8): 777-783

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中国药学杂志 | 综述 2025, 60(8): 777-783

肿瘤微环境中脂代谢与卵巢癌PARPi耐药相关机制的研究进展

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陈韦唯¹^,²^,³, 王琪¹^,²^,³^,^*

作者信息

¹ 广西医科大学附属肿瘤医院实验研究部, 南宁 530021

² 溶瘤纳米体系开发广西高校工程研究中心, 南宁 530021

³ 广西医科大学区域性高发肿瘤早期防治研究教育部重点实验室, 南宁 530021

陈韦唯,女,硕士研究生研究方向:卵巢癌耐药机制基础

通讯作者:

^*王琪,女,博士,教授研究方向:肿瘤分子分型与个体化治疗 Tel:(0771)5605960

Advances in Lipid Metabolism in the Tumor Microenvironment and Mechanisms Related to PARPi Resistance in Ovarian Cancer

Weiwei CHEN¹^,²^,³, Qi WANG¹^,²^,³^,^*

Affiliations

¹ Department of Experimental Research, Tumour Hospital of Guangxi Medical University, Nanning 530021 China

² University Engineering Research Center of Oncolytict and Naosyster Development, Nanning 530021 China

³ Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning 530021 China

出版时间: 2025-04-15 doi: 10.11669/cpj.2025.08.001

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摘要

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卵巢癌是一种女性死亡率较高的恶性肿瘤。多腺苷二磷酸核糖聚合酶抑制剂[poly (ADP-ribose) polymerase inhibitors, PARPi]作为维持治疗的主要手段之一,可显著提高患者的生存率,然而随着PARPi的广泛使用,PARPi耐药成为治疗过程中亟待解决的问题。目前研究发现肿瘤微环境(tumor microenvironment,TME)的代谢重编程可能通过多种机制影响卵巢癌化疗耐药,但TME中脂代谢重编程是否参与了PARPi耐药的形成尚不明确。本文旨在探讨近年来卵巢癌TME中脂代谢对PARPi耐药的影响,并分析其与PARPi耐药之间可能存在的联系,以期为进一步理解PARPi耐药形成机制和寻找新的治疗靶点提供新视角。

关键词

多腺苷二磷酸核糖聚合酶抑制剂耐药 / 脂代谢 / 卵巢癌 / 肿瘤微环境

Abstract

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Ovarian cancer is a malignant tumor with a high mortality rate in women. PARP inhibitors (poly ADP-ribose polymerase inhibitors, PARPi), as one of the mainstays of maintenance therapy, can significantly improve the survival rate of patients; however, with the widespread use of PARPi, PARPi resistance has become an urgent problem in the treatment process. Current studies have found that metabolic reprogramming in the tumor microenvironment (TME) may affect chemoresistance in ovarian cancer through multiple mechanisms, but whether lipid metabolic reprogramming in the TME is involved in the formation of PARPi resistance is not clear. The aim of this paper is to explore the effect of lipid metabolism in TME on PARPi resistance in ovarian cancer in recent years and to analyze the possible link between it and PARPi resistance, with a view to providing new perspectives for further understanding the mechanism of PARPi resistance formation and searching for new therapeutic targets.

Key words

PARP inhibitor resistance / lipid metabolism / ovarian cancer / tumor microenvironment

引用本文

陈韦唯, 王琪. 肿瘤微环境中脂代谢与卵巢癌PARPi耐药相关机制的研究进展. 中国药学杂志, 2025 , 60 (8) : 777 -783 . DOI: 10.11669/cpj.2025.08.001

Weiwei CHEN, Qi WANG. Advances in Lipid Metabolism in the Tumor Microenvironment and Mechanisms Related to PARPi Resistance in Ovarian Cancer[J]. Chinese Pharmaceutical Journal, 2025 , 60 (8) : 777 -783 . DOI: 10.11669/cpj.2025.08.001

正文

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根据国内癌症的最新数据统计,卵巢癌的发病率和死亡率位于女性肿瘤的前十位,因其恶性程度高及复发率高等因素,卵巢癌在女性生殖系统恶性肿瘤中的死亡率居首位^[1]。临床数据显示,在卵巢癌的维持治疗中使用多腺苷二磷酸核糖聚合酶抑制剂[poly (ADP-ribose) polymerase inhibitors,PARPi]能够显著延长患者的生存期,患者的5年无进展生存期(progression-free survival,PFS)延长至56.0个月,7年总生存期(overall survival,OS)达到67%^[2-3]。

在使用PARPi进行卵巢癌的维持治疗中,耐药问题逐步显现,主要表现为治疗效果降低、治疗选择受限,并可能对患者的生存期产生负面影响。因此,研究PARPi耐药机制对于增强PAPRi的抗癌效果具有重要意义,但目前PARPi耐药的机制研究并不完善,有研究表明肿瘤微环境(tumor microenvironment,TME)中的代谢重编程可影响肿瘤耐药的形成^[4-8],TME是指肿瘤细胞及肿瘤相关免疫细胞、肿瘤相关成纤维细胞(cancer-associated fibroblasts,CAF)、肿瘤相关脂肪细胞(cancer-associated adipocytes,CAA)及细胞因子等组成的一个微系统^[9-10],在TME中的各个细胞各司其职,却又通过代谢相互影响,如肿瘤相关巨噬细胞(tumor-associated macrophages,TAM),其可塑性强,可根据不同的影响因素转化成M1型及M2型TAM,TAM也能通过脂肪酸氧化(fatty acid oxidation,FAO)和脂肪酸合成途径影响脂代谢^[11-13]。脂代谢通过激活特定的信号传导途径[如核因子κB (nuclear factor κB,NF-κB)、磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,PI3K)丝氨酸/苏氨酸蛋白激酶B(protein kinase B,AKT)、Janus激酶(Janus kinase,JAK)/信号转导子和转录激活子(signal transducer and activator of transcription,STAT)等]促进脂肪合成,从而使DNA的复制增加,诱导卵巢癌对PAPRi及化疗药物等产生耐药^[14-18]。

笔者就卵巢癌TME中脂代谢与PARPi耐药之间可能存在的联系进行综述,将有助于为卵巢癌PARPi耐药的治疗提供新的靶点。

1 TME中脂代谢对PARPi耐药的调控机制

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1.1 TME可能参与PARPi耐药

PARPi的作用机制主要有两个方面:①抑制PARP1酶的活性;②将PARP1酶锁定在DNA损伤处,改变了PARP1酶的构象^[19-23]。PARP1酶的改变可以引发耐药,但PARPi耐药的原因不仅有PARP1酶的改变,还有同源重组(homologous recombination,HR)恢复、细胞内复制叉的稳定以及药物外排增加等^[24-26]。研究发现PARPi耐药与铂耐药之间存在密切联系,如HR恢复、多药耐药蛋白1(multidrug-resistance protein 1,MDR1)和P-糖蛋白(P-glycoprotein,P-gp)表达的升高既能导致细胞铂耐药,也能引起PARPi耐药,因此可以推断铂耐药的其他原因(如TME以及肿瘤自身的特异性)也可引起PARPi耐药^[27-28]。肿瘤细胞的特异性包括代谢重编程,肿瘤细胞能够通过代谢重编程影响其周围的TME以促进肿瘤细胞的增殖和耐药^[7,29]。随着肿瘤细胞的增殖,会引起TME中脂代谢的变化,生成的能量和营养物质不仅影响了肿瘤细胞还对TME中其他细胞的功能产生影响,从而影响整个肿瘤的生长和发展^[30-31]。TME中的脂代谢作为新兴的研究领域,包括脂质的摄取、合成、储存以及FAO等。在卵巢癌的转移和耐药过程中脂代谢发挥着重要的作用,卵巢癌细胞倾向于转移到富含脂肪的网膜处,这个区域能给脂代谢提供丰富的原料,有利于卵巢癌细胞进行脂代谢^[32-33],为卵巢癌细胞提供能量及生成细胞膜的原料^[34-35]。

脂代谢在DNA损伤修复中扮演着重要角色,FAO能生成活性氧(reactive oxygen species,ROS)和乙酰辅酶A(acetyl-coenzyme A,acetyl-CoA),ROS的过量积累会导致脂质过氧化,产生脂质过氧化物与DNA相结合可引起DNA氧化损伤或DNA单链断裂(single-strand break,SSB),而acetyl-CoA能促进PARP1的乙酰化进而支持DNA修复和基因组稳定性^[36-37],还能通过影响细胞信号传导通路[如PI3K/AKT、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等],间接影响DNA损伤修复。

以上研究表明,TME中脂代谢通过影响DNA的损伤修复使卵巢癌细胞增殖及PARPi耐药。因此,进一步探讨TME中脂代谢与卵巢癌PARPi耐药相关的机制对于开发新的治疗策略至关重要。靶向脂代谢也为研究人员提供了一个深入研究PARPi耐药机制的新方向,有望为治疗策略的优化和新药的开发提供重要参考。

1.2 CAF中的脂代谢对PARPi耐药的影响

CAF能通过脂代谢生成能量及脂质促进肿瘤细胞增殖,也可以通过分泌多种因子诱导肿瘤细胞对PARPi耐药。CAF的生成受许多因素影响,如肿瘤细胞释放转化生长因子-β(transforming growth factor-β,TGF-β)和溶血磷脂酸、白介素1(interleukin-1,IL-1)、白介素6(interleukin-6,IL-6)等因子,通过激活NF-κB、STAT通路使α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的表达增加和趋化因子配体5(C-C motif chemokine ligand 5,CCL5)因子分泌增多促使正常成纤维细胞(normal fibroblasts,NF)向CAF转化^[38-40]。脂肪酸合酶(fatty acid synthase,FASN)是脂代谢关键酶之一,在CAF中FASN的表达比NF高,其高表达可以促进CAF的脂代谢,脂代谢可以诱导CAF的代谢从糖酵解转变为脂代谢,形成脂代谢闭环^[41-42]。在脂代谢的作用下能将CAF分泌的乳酸盐转化为acetyl-CoA,增加游离脂肪酸(free fatty acid,FFA)的生成,促进脂滴形成和储存^[43],脂代谢还能使磷脂、甘油酯及磷脂酰胆碱生成增加,提高细胞膜的流动性和完整性促进肿瘤细胞转移^[42,44-45]。

卵巢癌微环境中的NF细胞不仅促进CAF的生成,还能通过旁分泌影响卵巢癌细胞HR功能,使卵巢癌细胞逃脱PARPi对细胞周期停滞的影响,诱发卵巢癌PARPi耐药。CAF受肿瘤细胞分泌细胞因子的影响,同时通过释放外泌体(extracellular vesicles,EV),增加TME中IL-6的含量从而诱导PARPi耐药,其主要机制如下:①激活JAK/STAT3信号通路导致肿瘤细胞的上皮-间质转化(epithelial-mesenchymal transition,EMT);②增加CD36的表达促进肿瘤细胞对脂质的摄取,以及细胞外基质(extracellular matrix,ECM)沉积,构成肿瘤细胞的物理屏障,减少药物与肿瘤细胞的接触;③触发CAF向衰老相关分泌表型(senescence-associated secretory phenotype,SASP)转化^[9,46-48]。

以上机制阐述了CAF与脂代谢及PARPi耐药之间错综复杂的关系,CAF既能通过脂代谢生成脂质参与肿瘤细胞增殖,还能通过释放相关因子(IL-6等)诱导PARPi耐药,虽然目前CAF脂代谢引起PARPi耐药的机制尚不明确,但有研究发现PARPi耐药细胞中环氧化酶-2(cyclooxygenase-2,COX-2)表达升高,二甲双胍通过抑制CAF中NF-κB信号通路,减少IL-6及COX-2的释放,而抑制或敲除COX-2能让耐药细胞对PARPi及化疗药物重新敏感^[49-50]。因此针对CAF的脂代谢进行干预,有助于抑制肿瘤细胞增殖,并开发新的治疗策略来克服CAF脂代谢引起的PARPi耐药。

1.3 TAM中脂代谢参与PARPi耐药的机制

TAM的极化表型是导致肿瘤多种治疗耐药的原因之一,M2型TAM的极化受肿瘤细胞分泌集落刺激因子1(colony-stimulated factor 1,CSF-1)、IL、TGF-β等因子影响,M2型TAM的极化还受脂代谢的影响,且M2型TAM能通过脂代谢为肿瘤细胞提供生长原料使其迅速增殖。M2型TAM因富含脂质及脂代谢相关基因[肉碱棕榈酰转移酶1(carnitine palmitoyltransferase 1,CPT1)]、脂代谢关键调节因子过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)高表达等因素,推动了脂代谢的发生,并激活PPAR通路增加CD36的表达,促进肿瘤细胞对脂肪酸(fatty acid,FA)的摄取,刺激肿瘤细胞增殖^[13,51-54]脂代谢,还影响M2型TAM激活STAT信号通路上调CD36表达,增强TAM及肿瘤细胞对脂质的摄取,保持线粒体的完整性,阻止化疗诱导的肿瘤细胞凋亡,CD36摄取FFA后激活肿瘤细胞中的无翅型MMTV整合位点家族(wingless-type MMTV integration site family,Wnt)/TGF-β通路引起EMT,导致肿瘤细胞增殖和耐药^[32,55-56]。

M2型TAM促进脂代谢的同时也能影响肿瘤细胞耐药。M2型TAM分泌的EV可通过增加分泌IL-6及CCL4因子,激活CCR5/PI3K信号通路使卵巢癌耐药细胞分泌EV将化疗药物排出细胞外,再通过内吞作用进入正常肿瘤细胞,传递耐药表型形成耐药循环^[12,57],IL还可以通过激活PI3K/AKT通路诱导耐药^[28-29]。随着IL-6分泌的增多,激活了STAT/NF-κB信号通路加速TAM极化为M2型,增加脂代谢相关蛋白的表达,使卵巢癌细胞对PARPi耐药^{[14-15,58-61]}。而TAM细胞膜上的ATP结合盒式(ABC)转运蛋白高表达,也能激活JAK/STAT信号通路,促使脂筏、胆固醇从TAM中流出,激活PI3K/AKT信号通路,促进肿瘤增殖及耐药。

M2型TAM的极化与脂代谢之间形成正反馈的同时,还通过分泌IL和TGF-β等免疫抑制因子,生成一个抑制免疫反应的微环境,从而促使PARPi耐药的产生,若缺乏CD36可导致TAM分化为M1型^[62]。因此靶向TAM的脂代谢及脂代谢相关因子/蛋白如FASN、CPT1、线粒体延伸因子2(mitochondrial elongation factor 2,MIEF2)、硬脂酰辅酶A去饱和酶1(stearoyl-coa desaturase 1,SCD1)、脂肪酸结合蛋白4(fatty acid binding protein 4,FABP4)、COX-2等能为治疗卵巢癌PARPi耐药提供新方案。

1.4 TME中其他细胞脂代谢与PARPi耐药之间存在联系

在脂代谢的作用下,TME中的其他细胞参与脂代谢并生成肿瘤细胞合成原料,促进肿瘤细胞增殖及导致PARPi耐药。脂肪来源干细胞(adipose-derived stem cells,ADSCs)受到脂代谢影响使FABP4、PARP1表达增加可加速ADSC分化为CAA促进肿瘤细胞增殖,但癌细胞和药物对ADSC的影响会改变ADSC旁分泌信号导致肿瘤细胞耐药^[63-64]。在肿瘤细胞刺激下CAA能分泌大量的细胞因子(如瘦素、IL等)和EV共同推进脂代谢的发生,CAA还可使CPT1表达升高,通过脂代谢推动线粒体外的酰基辅酶A转化为酰基肉碱,与酰基肉碱转位酶(carnitine acylcarnitine translocase,CACT)相结合穿过线粒体内膜并还原为酰基辅酶A参与FAO生成FA,诱导肿瘤细胞增殖^[65-66]。IL-6激活STAT通路及升高CD36表达,使摄取的FA参与FAO转化为acetyl-CoA、甘油三酯及能量,acetyl-CoA进入三羧酸循环(tricarboxylic acid cycle,TCA)产生ATP并进行脂肪酸从头合成,参与肿瘤细胞细胞膜的合成^[4,8,56-67]。而EV可以通过脂代谢诱导卵巢癌紫杉醇耐药^[68]。

脂代谢异常会直接或间接地影响肿瘤局部免疫微环境中的T淋巴细胞,如FFA的积累会破坏CD4⁺T细胞的线粒体并使ROS增加,FFA积累还能使髓源性抑制细胞(myeloid-derived suppressor cells,MDSC)将其使用为生物合成原料,促进细胞内脂滴形成,CD8⁺T细胞内的胆固醇积累能触发内质网应激诱导CD8⁺T细胞中程序性死亡蛋白-1(programmed death-1,PD-1)、信号淋巴细胞激活分子家族成员4、T细胞免疫球蛋白黏蛋白分子3(T cell immunoglobulin and mucin-containing molecule 3,TIM-3)和淋巴细胞活化基因-3(lymphocyte activation gene-3,LAG-3)的表达,使CD8⁺T细胞呈现出功能耗竭与免疫抑制状态^[69]。T细胞活性还受细胞程序性死亡配体-1(programmed cell death ligand 1,PD-L1)影响,MDSC通过FAO合成PD-L1、TAM能分泌表面富含PD-L1蛋白的EV,使PD-L1与CD8⁺T细胞上的PD-1结合,从而抑制T细胞的活性^[10,70],将TAM分泌表面富含PD-L1蛋白的EV与CD8⁺T细胞共培养时通过PPARα信号通路催化脂肪酸形成酰基辅酶A及上调CPT1 A表达促进FAO,增加活性氧,诱导CD8⁺T细胞凋亡^[71]。T细胞活性还受到MDSC的影响,伏隔核相关蛋白1(nucleus accumbens-associated protein 1,NAC1,在卵巢癌细胞中高表达)通过与C-X-C基序趋化因子受体6(C-X-C motif chemokine receptor 6,CXCR6)结合增强C-X-C基序趋化因子配体16(C-X-C motif chemokine ligand 16,CXCL16)的表达募集MDSC,卵巢癌细胞分泌CCL2、CCL5等趋化因子也能招募MDSC,MDSC增多可抑制CD8⁺T细胞的活性,影响树突细胞抗原呈递^[72]。MDSC和调节性T细胞(regulatory T cells,Tregs)通过免疫细胞和肿瘤细胞之间相互作用,促使免疫抑制环境形成,降低了PARPi敏感性,值得注意的是,MDSC表达PARP1的水平相对较低,这为其逃避PARPi的作用提供了有利条件^[59,73-74]。在肿瘤的局部免疫微环境中,T淋巴细胞、MDSC、TAM之间形成了错综复杂的相互作用网络。这些关键的免疫细胞群体之间的密切互动共同塑造了肿瘤细胞的增殖行为和对PARPi的耐药性。

以上研究阐述了TME中的组成细胞受到肿瘤细胞释放IL、TGF-β等因子的影响后,通过激活NF-κB、STAT、PI3K、AKT通路增加了CAF生成及M2型TAM极化促进脂代谢,脂代谢不仅能生成大量的能量及脂质也影响脂代谢相关基因的表达最终导致PARPi耐药。这些机制表明,TME中的脂代谢能通过多种途径影响卵巢癌对PARPi的敏感性,为了解PARPi耐药机制提供了重要线索。然而,这一领域的研究仍处于起步阶段,需要更多的研究来深入探讨TME中的脂代谢调控PARPi耐药机制以达到逆转PARPi耐药的目的。

2 靶向脂代谢或将成为PARPi耐药的潜在治疗策略

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脂代谢可能是PARPi耐药治疗的新靶点之一,目前针对脂代谢的靶向药在基础研究阶段已取得一定的成功,这些研究大部分针对脂代谢相关因子,并通过抑制其活性来达到抑制肿瘤生长及逆转耐药目的。

脂代谢靶向药物及其组合可以通过不同机制抑制肿瘤细胞增殖及促使肿瘤细胞凋亡。脂代谢因子在脂代谢中通过多种机制影响脂肪的合成、分解以及能量平衡,如①MIEF2激活ROS/ AKT/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号增加了脂肪酸合成酶(SCD1、FASN)的表达,促进卵巢癌细胞的生长和转移,敲除MIEF2导致G1/S细胞周期停滞、EMT诱导细胞凋亡^[75-76];②SCD1参与细胞膜磷脂的合成,通过影响TME中的免疫细胞和基质细胞,导致卵巢癌耐药^[77]。有研究证明,SCD1抑制剂通过激活AMPKα通路使SCD1的表达降低,抑制卵巢癌细胞增殖和增加PARPi对卵巢癌铂耐药细胞的凋亡作用,还发现SCD1抑制剂CAY10566和脂肪酸去饱和酶2抑制剂sc26196与顺铂联合使用可使卵巢癌细胞G1/S细胞周期停滞及凋亡^[78-80];③FASN在CAF中的高表达会影响脂代谢及PARPi耐药,而降低FASN的表达可以激活细胞早期自噬及抑制晚期自噬导致卵巢癌细胞死亡^[81]。FASN抑制剂TVB-2640与紫杉醇在临床上首次联合使用时发现,两者联合可使卵巢癌部分缓解(partial response,PR)^[82];④CPT1抑制剂既能够通过影响T细胞代谢和阻断脂肪酸氧化来抑制肿瘤生长,也能使铂耐药细胞重新对铂敏感,因此其与铂类药物联合使用时耐药细胞凋亡效果更显著^[83-85];⑤FABP4抑制剂能减少卵巢癌转移,与卡铂联合使用可使耐药细胞对卡铂重敏感;⑥COX-2抑制剂和顺铂联合使用也可抑制耐药及部分逆转耐药^[86]。

目前,影响脂质代谢的常见药物包括他汀类、贝特类、烟酸类及二甲双胍等。已有研究证明他汀类药物能通过改善脂代谢而延长卵巢癌患者的OS,二甲双胍可降低卵巢癌患者死亡率^[87-88]。尽管目前没有明确的指南推荐脂代谢药物可作为PARPi耐药的一线用药,但有许多临床试验发现二甲双胍与卡铂/紫杉醇联合使用能增强化疗效果,Broekman等^[89]Ⅰ期临床研究发现联合治疗时并未出现二甲双胍相关剂量限制性毒性,二甲双胍在联合治疗中的安全性得到了初步验证,Micha等^[90]Ⅱ期临床试验发现,联合用药的中位OS为35个月的,其中毒性作用为3%的人出现3级血小板减少,43.3%的人出现3~4级中性粒细胞减少症,表示二甲双胍具有较好的耐受性,并能增强铂类和紫杉类化疗的疗效。Xie等^[91]发现二甲双胍联合用药的耐药率明显低于安慰组(未使用二甲双胍),且3年总生存率较高,二甲双胍联合用药在提高生存率和降低耐药性方面显示出积极效果。

尽管目前缺乏靶向脂代谢药物逆转PARPi耐药的临床试验,但多项临床试验表明,二甲双胍与卵巢癌一线化疗联合使用具有良好的耐受性和潜在的治疗增效作用。并且临床前研究发现通过抑制脂肪酸合成、脂肪酸氧化以调节脂代谢不仅可以抑制肿瘤生长还能逆转耐药以使耐药细胞重敏感,这些研究结果为未来进一步探索脂代谢药物在治疗卵巢癌PARPi耐药中的应用提供了有力的支持。

3 结语与展望

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TME中的细胞因脂代谢相关基因/蛋白表达的增多及受到肿瘤细胞释放因子等因素的影响,激活脂代谢可以给肿瘤细胞提供大量细胞合成原料及能量,推动肿瘤细胞生长、耐药。因此,笔者推测脂代谢可能成为治疗或缓解PARPi耐药的新靶点,为未来治疗策略的制定提供了新的思路。目前没有直接证据表明TME中的脂代谢可以直接导致PARPi耐药,并且缺乏靶向脂代谢对PARi耐药的临床研究,但通过分析TME与脂代谢之间的联系以及TME与PARPi耐药之间的关系,可以发现它们之间可能通过多种途径存在间接或直接联系(图1)。TME中脂代谢可成为研究PARPi耐药的新方向,并有助于开发针对脂代谢途径的新治疗策略,以提高卵巢癌患者的治疗效果和生存质量。

基金

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国家自然科学基金项目资助(82260484)
区域性高发肿瘤早期防治研究教育部自主研究项目资助(GKE-ZZ202236)

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2025年第60卷第8期

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doi: 10.11669/cpj.2025.08.001

接收时间：2024-09-05
首发时间：2025-11-12
出版时间：2025-04-15

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收稿日期：2024-09-05

基金

国家自然科学基金项目资助(82260484)

区域性高发肿瘤早期防治研究教育部自主研究项目资助(GKE-ZZ202236)

作者信息

¹ 广西医科大学附属肿瘤医院实验研究部, 南宁 530021

² 溶瘤纳米体系开发广西高校工程研究中心, 南宁 530021

³ 广西医科大学区域性高发肿瘤早期防治研究教育部重点实验室, 南宁 530021

通讯作者:

^*王琪,女,博士,教授研究方向:肿瘤分子分型与个体化治疗 Tel:(0771)5605960

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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